The present invention pertains to biosensors based on uniquely designed polymer optical waveguides that are adaptable to a variety of environments, and to both chemical and biological species. In particular, the invention relates to polymer-based, index of refraction-mediated analyte sensing devices.
Diagnostics is a rapidly growing field with medical, agricultural, environmental, and industrial markets. In the field of diagnostics, robust, low-cost, target-specific sensors play critical roles. In medicine, devices tailored to monitor for levels of substances in situ (e.g., sensing specific toxins, metabolites, etc., are of great value). In manufacturing or environmental contexts, such devices are employed for effluent monitoring, and in the detection of either inorganics or organics, to name but a few applications.
The potential of the market for specialty analytical technologies is suggested by an example from the health care industry, where a single category of diagnostic/testing devicesxe2x80x94for monitoring glucose in diabetes management/self-managementxe2x80x94is currently a $2 billion worldwide market, with an annual growth rate of 10-15% (xe2x80x9cBusiness Review with Tom Hodgsonxe2x80x9d, Abbott World (1997) 4-7). Other analytical demands, e.g., for the discrimination between each of the enantiomers in the preparation of a chiral pharmaceutical, have been clearly ordained, and have yet to have their full impact on the marketplace (Casy, The Steric Factor in Medicinal Chemistry: Dissymmetric Probes of Pharmacological Receptors, (New York: Plenum Press, 1993)). The need for analytical technologies underlies:
(1) the traditional and well-developed chromophore-, fluorophore-, etc. based methods (Blum et al., eds. Biosensor Principles and Application Bioprocess Technology, Vol. 15, (NY: Marcel Dekker, 1991); Rogers et al., eds. Biosensor and Chemical Sensor Technology, ACS Symposium Series 613 (Washington, D.C.: American Chemical Society, 1995); Mathewson et al., eds. Biosensor Design and Application, ACS Symposium Series 511 (Washington, D.C., American Chemical Society, 1992));
(2) more recent electrochemical efforts (including xe2x80x9creceptorxe2x80x9d-modified electrodes) (Blum et al., supra; Rogers et al, supra; Mathewson et al, supra); and (3) inroads into solid-state analyte sensing technologies (Blum et al, supra).
The limitations inherent to each of these methods have been given considerable attention in efforts to meet the demands of the diagnostic field (Katzir, ed. Lasers and Optical Fibers in Medicine, (NY: Academic, 1993) 204; McCurley et al., xe2x80x9cFiber-Optic Sensor for Salt Concentration Based on Polymer Swelling Coupled to Optical Displacementxe2x80x9d, Anal. Chim. Acta., 249 (1991) 373-380). Medical diagnostic sensors which make use of fiberoptic components also have received increasing attention. Unfortunately, their inherent limitationsxe2x80x94with respect to optode construction, calibration, sensitivity, chemical stability, response time, and dynamic rangexe2x80x94have yet to be fully resolved (Katzir, supra; Rouhi, xe2x80x9cBiosensors Send Mixed Signalsxe2x80x9d, CandEN, (May 12, 1997) 41-45). As such, there is yet need for new analytical devices which address some or all of these shortcomings in prior devices.
The sensing devices of almost all common electronic and photonic instruments are currently based on inorganic materials, including biosensors (e.g., the inorganic fiber-optic- and silicon-based Mach-Zehnder interferometer) (xe2x80x9cLaser Focus Worldxe2x80x9d, (December 1996) 66). However, more recently, organic non-polymeric and polymeric materials have begun to emerge as potential chemical systems suitable for discrete sensing. In the 1990""s, polymeric-based interferometer and other devices generated great interest (Girton et al., xe2x80x9cElectrooptic Polymer Mach-Zehnder Modulatorxe2x80x9d, In ACS Symposium Series 601, Polymers for Second Order Nonlinear Optics (Washington, D.C., 1995) 456-468). The organic polymeric materials exhibit physical and chemical xe2x80x9cflexibilityxe2x80x9d, and, for instance, can be relatively easily chemically modified to suit specific applications. This flexibility eases their fabrication (e.g., into integrated optical circuitry) which contributes to lower costs of manufacture. The flexibility promotes rapid cycles of material design, preparation, testing, and redesign. Polymer-based devices could ultimately be mass-produced using simple printing processes. Moreover, organic polymers provide a large inventory of photonic materials that have a low dielectric constant. Certain of the polymers show high stability and optical nonlinearity.
Polymeric materials have more recently emerged as materials for use in optical applications (Keil, xe2x80x9cRealization of IO-Polymer-components and Present State in Polymer Technologyxe2x80x9d, In Integrated Optics and Micro-Optics with Polymers, (Stuttgart-Leipzig: B. G. Teubner Verlagsgesellschaft, 1993) 273; Ito et al., eds. Polymeric Materials for Microelectronic Applications, ACS Symposium Series 579 (Washington, D.C.: American Chemical Society, 199); Lindsay et al., eds., Polymers for Second Order Nonlinear Optics, ACS Symposium Series 601 (Wash., D.C.: American Chemical Society, 1995) pp. 1, 111, 130, 158, 172, 347, 381; Edelman et al., eds. Biosensors and Chemical Sensors, ACS Symposium Series 487 (Wash., D.C.: American Chemical Society, 1992)). The tremendous excitement in industry regarding these new materials suggests polymeric materials will survive to compete with well established and low cost inorganic materials. (Levenson et al., xe2x80x9cAdvances in Organic Polymer-Based Optoelectronicsxe2x80x9d In ACS Symposium Series 601, Polymers for Second Order Nonlinear Optics, G. A. Lindsay and K. D. Singer, eds., (Washington, D.C.: American Chemical Society, 1995)).
Among the more recently developed polymeric materials are polyimides that have been demonstrated to have superior optical and physical characteristics. In particular, certain polyimides show thermal stability, as well as high optical nonlinearity (as reflected in their r33 values) (Lindsay et al., supra). W. R. Seitz, commenting on related work from the 1980""s, noted the potential for xe2x80x9crugged and inexpensivexe2x80x9d sensors based on devices which monitor the change in the index of refraction on transmission of light through such an optical component (McCurley et al., supra). Traditionally, Seitz notes, such applications have been limited by a lack of selectivity, leading once again to reliance upon the optical properties of the analyte per se.
The present invention accordingly seeks to overcome these deficiences in the prior art by providing a novel class of waveguide sensors that employ a variant of a recently developed polyimide polymers that is uniquely engineered to allow modification by recognition elements (i.e., concurrent with or following device fabrication). The recognition element-analyte tests provided by the sensors can accommodate a range of analytes (e.g., inorganic and organic, polar and apolar, low and high molecular weight). These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the following description of the invention provided herein.
The present invention provides inter alia biosensors that are based on uniquely designed polymer optical waveguides that are adaptable to a variety of environments, and to both chemical and biological species. In particular, the invention provides polymer-based, index of refraction-mediated analyte sensing devices.